Small Aliphatic Dicarboxylic Acids Inhibit Renal Uptake of Administered Mercury

Zalups, Rudolfs K.; Barfuss, Delon W.

doi:10.1006/taap.1997.8320

Cited by 36 publications

(26 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, the four-carbon dicarboxylate succinate is not an effective inhibitor of OAT1 (32). In a recent study, it was demonstrated that both adipate and glutarate but not succinate or malonate (three-carbon atoms long), inhibited (in a dose-dependent manner) the uptake of intravenously administered Hg 2ϩ in rats (8). These findings are in complete agreement with those of the present investigation.…”

Section: Discussionsupporting

confidence: 92%

“…preponderance of this accumulation occurring in proximal tubular epithelial cells (1,(22)(23)(24). At least one luminal mechanism and at least one basolateral mechanism have been shown to be responsible for the uptake of mercuric ions by proximal tubular epithelial cells (5)(6)(7)(8)(9)(10)(11)(12)(13)25,26).…”

Section: Discussionmentioning

confidence: 99%

“…Because PAH is a high-affinity substrate of the OAT1 (27,28), we postulated that OAT1 is involved in the basolateral uptake of Hg in vivo (5)(6)(7)(8)(9)(10)(11)(12)(13)25,26).…”

Section: Discussionmentioning

confidence: 99%

“…It is interesting that current evidence indicates that there are indeed both luminal and basolateral mechanisms involved in the proximal tubular uptake and accumulation of Hg (1). Several lines of evidence have emerged indicating that mercuric conjugates of cysteine (Cys), in the form of 2-amino-3-(2-amino-2-carboxy-ethylsulfanylmercuricsulfanyl) propionic acid (Cys-S-Hg-S-Cys), are substrates that can be taken up from the blood and extracellular fluid by proximal tubular epithelial cells at their basolateral membrane by one or more organic anion transport systems (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The most conclusive evidence implicating the organic anion transporters has come recently from two studies that used type II MDCK cells transfected stably with the human isoform of oat1.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Homocysteine and the Renal Epithelial Transport and Toxicity of Inorganic Mercury

Zalups

Ahmad²

2004

Journal of the American Society of Nephrology

100

View full text Add to dashboard Cite

Abstract. The epithelial cells that line the renal proximal tubule have been shown to be the primary cellular targets where mercuric ions gain entry, accumulate, and induce pathologic effects in vivo. Recent data have implicated at least one of the organic anion transport systems in the basolateral uptake of inorganic mercury (Hg). With the use of a line of type II MDCK cells transfected stably with the human organic anion transporter 1 (hOAT1), the hypothesis that hOAT1 can transport mercuric conjugates of homocysteine (Hcy) was tested. Indeed, MDCK II cells expressing a functional form of hOAT1 gained the ability to transport the mercuric conjugate 2-amino-4-(3-amino-3-carboxy-propylsulfanylmercuricsulfanyl) butyric acid (Hcy-S-Hg-S-Hcy). In addition, p-aminohippurate and the dicarboxylates adipate and glutarate (but not succinate or malonate) inhibited individually the uptake of Hcy-S-Hg-S-Hcy in a concentration-dependent manner. Furthermore, a direct relationship between the uptake of Hcy-S-Hg-S-Hcy and the induction of cellular injury and death was demonstrated in the hOAT1-expressing MDCK II cells only. These data represent the first line of direct evidence implicating one of the organic anion transporters in the uptake of a mercuric conjugate of Hcy in a mammalian cell. Thus, mercuric conjugates of Hcy are potential transportable substrates of OAT1. More important, the findings from the present study implicate the activity of OAT1 in the uptake and toxicity of Hg (when in the form of Hcy-S-Hg-SHcy in the extracellular compartment) in proximal tubular epithelial cells in vivo.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

“…Because PAH is a high-affinity substrate of the OAT1 (27,28), we postulated that OAT1 is involved in the basolateral uptake of Hg in vivo (5)(6)(7)(8)(9)(10)(11)(12)(13)25,26).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Homocysteine and the Renal Epithelial Transport and Toxicity of Inorganic Mercury

Zalups

Ahmad²

2004

Journal of the American Society of Nephrology

100

View full text Add to dashboard Cite

show abstract

“…Adipic acid and succinic acid inhibit renal uptake of mercury in rats by inhibiting the organic anion transporter [31]. Inhibition of ceftibuten by adipic acid seems to suggest that Caco-2 cells express the anionic transporter responsible for dicarboxylic acid transport.…”

Section: Discussionmentioning

confidence: 98%

Transporters involved in apical and basolateral uptake of ceftibuten into Caco‐2 cells

Menon

Barr

2002

Biopharm & Drug Disp

View full text Add to dashboard Cite

Ceftibuten uptake from the apical and basolateral side of Caco-2 cells grown on transwells was studied. Uptake into the cells showed concentration dependent saturation. The apical transporter(s) showed a higher capacity and lower affinity for ceftibuten than the basolateral transporter(s). Uptake was inhibited in the presence of higher pH and in the presence of 2,4-dinitro phenol (DNP). A proton gradient had a greater effect on the apical than on the basolateral transporter. Glycyl proline, a dipeptide transport system (PEPT1) substrate, inhibited ceftibuten uptake into Caco-2 cells. Benzoic acid, a monocarboxylic acid (MCT) transporter substrate also exhibited a strong inhibition of ceftibuten uptake, but acetic acid had no effect. Adipic acid inhibited apical uptake of ceftibuten but had no effect on the basolateral uptake. None of the inhibitors had a significant effect on ceftibuten uptake in absence of a pH gradient. Addition of inhibitors in presence of DNP led to a greater decrease in ceftibuten uptake, when compared to the effect of DNP alone, indicating a facilitated diffusion process. These results indicate that ceftibuten uptake in Caco-2 cells involve multiple transport pathways. Apical uptake is mediated by an energy dependent carrier-mediated process and an energy independent facilitated diffusion process. The apical transport system is different from the basolateral transporter.

show abstract

Basolateral Uptake of Inorganic Mercury in the Kidney

Zalups

1998

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Small Aliphatic Dicarboxylic Acids Inhibit Renal Uptake of Administered Mercury

Cited by 36 publications

References 16 publications

Homocysteine and the Renal Epithelial Transport and Toxicity of Inorganic Mercury

Homocysteine and the Renal Epithelial Transport and Toxicity of Inorganic Mercury

Transporters involved in apical and basolateral uptake of ceftibuten into Caco‐2 cells

Basolateral Uptake of Inorganic Mercury in the Kidney

Contact Info

Product

Resources

About